This invention relates to compositions adaptable to terminating a pregnancy of a higher female primate having a defined menstrual or estrous cycle by administration to the pregnant female of a contragestative agent, which has estrogen sulfotransferase inhibitory activity and which prevents implantation.
The use of chemical agents to prevent or suppress fertility in warm-blooded female mammals is widely practiced in the medical art. The most widely used of these chemical agents comprise mixtures of steroidal estrogens and progestins. These agents produce a type of pseudopregnancy which prevents normal ovulation from occurring in the female taking the medication. Although these agents are very effective, noticeable and irritating side effects, including nausea, gastric disturbances, headache, dizziness, breast discomfort, fluid retention, and vascular disorders, are often produced.
Contraception has also been brought about by impairing the luteal phase of the endometrium. A properly prepared endometrium or uterine lining is required for the blastocysts to become successfully implanted. Agents can act either to interfere with the formation of the luteal or secretory phase of the endometrium. In an alternate mode of action agents delay or decrease formation of the luteal phase of the uterine lining. The result is desynchronization of uterine development with respect to blastocyst implantation or nidation.
Intrauterine devices of various kinds have also been used to prevent pregnancy. These devices must be inserted by qualified medical practitioners. Moreover, they are not totally reliable as a means of preventing pregnancy because intrauterine devices can be involuntarily expelled without knowledge of the patient. In other cases the devices may cause intrauterine irritation or bleeding.
Another type of contraceptive practice known to the medical profession is administration of an estrogen, e.g., diethylstilbesterol or ethinyl estradiol. These are the so-called "morning-after pill," because they are used as post-coital contraceptive agents. These agents are thought to be effective because they interfere with the transport mechanism of the fertilized ovum through the Fallopian tubes and result in premature expulsion of the fertilized ovum (blastocyst) from the Fallopian tubes or because they reverse the differentiation of the endometrium from secretory back to proliferative.
Because of the annoying and sometimes serious side effects of currently used anti-fertility agents, there is a need for chemical agents which will prevent pregnancy and for new and better methods of administering existing anti-fertility agents. Particularly, there is a need for highly effective compounds which can be administered to a female patient who suspects that she is in the early stages of pregnancy, but which otherwise requires minimal exposure of the patient to powerful steroidal medication.
It is an object of this invention to provide highly effective contragestative agents for higher primates having a well-defined menstrual or estrous cycle. These compounds are therefore effective for terminating pregnancies at a very early stage. Unlike widely used "pill" formulations, which must be administered in anticipation of coitus, the compounds used in the method of the present invention are administered only when needed and then only for a relatively short time before or at the expected time of implantation.